An overview of the importance of conformational flexibility in gene regulation by the transcription factors

Abstract

A number of proteins with intrinsically disordered (ID) regions/domains are reported to be found disproportionately higher in transcription factors. Available evidences suggest that presence of ID region/domain within a transcription factor plays an important role in its biological functions. These ID sequences provide large flexible surfaces that can allow them to make more efficient physical and functional interactions with their target partners. Since transcription factors regulate expression of target genes by interacting with specific coregulatory proteins, these ID regions/domains can be used as a platform for such large macromolecular interactions, and may represent a mechanism for regulation of cellular processes. The precise structural basis for the function of these ID regions/domains of the transcription factors remains to be determined. In the recent years there has been growing evidence suggesting that an induced fit-like process leads to imposition of folded functional structure in these ID domains on which large multiprotein complexes are built. These multiprotein complexes may eventually dictate the final outcome of the gene regulation by the transcription factors.

Figure 1

A model showing possible events/factors that may alter conformation of an ID domain/region of transcription factors to fold into a functionally active form. (a) An ID domain/region without any defined structure ((a) blue) may adopt a set of partially folded conformation ((b) red) due to specific events/factors shown here. This conformation may suit well for specific interactions with binding partners (purple) and result in functionally active conformation ((c) green) under physiological conditions.